High efficiency of ROS production by glycerophosphate dehydrogenase in mammalian mitochondria.
We investigated hydrogen peroxide production in mitochondria with low (liver, heart, brain) and high (brown adipose tissue, BAT) content of glycerophosphate dehydrogenase (mGPDH). ROS production at state 4 due to electron backflow from mGPDH was low, but after inhibition of electron transport with antimycin A high rates of mGPDH-dependent ROS production were observed in liver, heart and brain mitochondria. When this ROS production was related to activity of mGPDH, many-fold higher ROS production was found in contrast to succinate- (39-, 28-, 3-fold) or pyruvate plus malate-dependent ROS production (32-, 96-, 5-fold). This specific rate of mGPDH-dependent ROS production was also exceedingly higher (28-, 66-, 22-fold) compared to that in BAT. mGPDH-dependent ROS production was localized to the dehydrogenase+CoQ and complex III, the latter being the highest in all mitochondria but BAT. Our results demonstrate high efficiency of mGPDH-dependent ROS production in mammalian mitochondria with a low content of mGPDH and suggest its endogenous inhibition in BAT.
Mrácek
Tomás
T
Department of Bioenergetics, Institute of Physiology and Center for Applied Genomics, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, Czech Republic.
Pecinová
Alena
A
Vrbacký
Marek
M
Drahota
Zdenek
Z
Houstek
Josef
J
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D006224:Cricetinae; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism
D017382:Reactive Oxygen Species; D000968:Antimycin A; D019289:Pyruvic Acid; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D005993:Glycerolphosphate Dehydrogenase; D014450:Electron Transport Complex III